The State of Differentiation of Embryonic Chicken Lens Cells Determines Insulin-Like Growth Factor I Internalization*

Abstract
Microdissected epithelial cells from chicken embryonic lens differentiate into fiber cells during primary culture. Binding of IGF-I to both cell types has been documented biochemically. This report describes differences in the internalization of insulin-like growth factor I (IGF-I) in the two cell types using three electron microscopic approaches. Cells were incubated with a biologically active colloidal gold-labeled-IGF-I complex or [125I]IGF-I and prepared for electron microscopy. Other cells were incubated with unlabeled IGF-I and prepared for immunoelectron microscopy, using a colloidal gold-labeled anti-IGF-I antibody to detect the IGF-I. Each technique demonstrated binding of IGF-I on the surface of epithelial and differentiated fiber cells. IGF-I was internalized in epithelial cells. In contrast, the ligand exhibited little endocytosis in fiber cells during a 5 h incubation. Intracellular IGF-I was observed in the endosomes, Golgi apparatus, and lysosomes of epithelial cells, in addition, it was shown for the first time that IGF-I was translocated to the nucleus of epithelial cells. The differences between epithelial and fiber cells regarding internalization and nuclear translocation of IGF-I suggest that there are cell-specific itineraries of the hormone, depending on the differentiation stage of the cell. These differences may relate to the specific biological actions of the growth factor on each of these cells, particularly in allowing proliferation and differentiation of the epithelial cells.